Device for administration to ruminants

ABSTRACT

A device for administering a therapeutic or nutrient substance to a ruminant over an extended period of time, comprising at least one body portion containing or comprising said substance and having a first configuration or being adapted to be arranged in a first configuration, whereby it is adapted to be administered per os so as to pass into the rumen and being adapted to change in the rumen into a second configuration which will prevent or at least hinder regurgitation of the device, whereby the device is retained in the rumen. The device is especially useful in the treatment of bovine bloat by extended release in the rumen of surface active substances.

United States Datent [191 Laby [ DEVICE FOR ADMINISTRATION TO RUMINANTS[75] Inventor: Ralph Henry Laby, Victoria,

Australia [73] Assignee: Commonwealth Scientific and Industrial ResearchOrganization, Campbell, Australia [22] Filed: Dec. 14, 1972 [21] Appl.No.: 315,013

Related US. Application Data [63] Continuation of Ser. No. 67,955, Aug.28, 1970,

abandoned.

[52] US. Cl. 128/260 [51] Int. Cl A6lm 31/00 [58] Field of Search128/260, 272, 130, 213,

[56] References Cited UNlTED STATES PATENTS 462,990 11/1891 Oppenheimer128/272 X 1,957,564 5/1934 West 128/272 2,580,414 1/1952 Duffey 206/843,118,439 1/1964 Perrenoud 128/260 X 3,136,695 6/1964 Tansey 424/223,247,066 4/1966 Milosovich, .lr. 424/37 X 3,315,660 4/1967 Abella128/260 X 3,463,745 8/1969 Hofrichter 128/127 X 3,507,952 4/1970 Rednicket a1 424/22 3,545,439 12/1970 128/260 3,577,513 5/1971 Roebuck et a1424/22 Primary ExaminerRichard A. Gaudet Assistant Examiner-J. C.McGowan Attorney, Agent, or Firm-Bacon & Thomas [57] ABSTRACT The deviceis especially useful in the treatment of bovine bloat by extendedrelease in the rumen of surface active substances.

18 Claims, 13 Drawing Figures PAIENTEMMQ m4 3.844.285 sum 2 0F 3 Rr 6mB/Ww E w W MW M H m6 av R5 PAIENIEDums m4 3l844l285 am an 3 nvvew r02Rem HEN/er Mar TTORNEYS 1 DEVICE FOR ADMINISTRATKON TO RUMINANTS This isa continuation, of application Ser. No. 67,955, filed Aug. 28, i970, nowabandoned.

, This invention relates to devices suitable for administering toruminants. More particularly, it relates to devices useful forpreventing bloat in bovines, and for preventing other disorder ofruminants for which reticulorumen (hereinafter abbreviated to rumen)infusion of an effective curative or control agent over an extendedperiod of time would be an advantage. Whilst particular reference ismade hereinafter to devices for the prevention of bloat, it will beunderstood that these devices are equally applicable to the preventionof these other disorders. Thus, for example, the devices describedherein provide a means for the perfusion into the rumen of thetherapeutic substances, metal salts for the correction of deficiencydiseases, or nutrients or other agents which may be of advantage forhealthy stock.

Bovine bloat is characterized by distension of the animals rumen andresults from the formation of a stable foam above the rumen liquor whichprevents the escape of gases produced by the micro-organisms in therumen. Cattle feeding on fresh clover are particularly prone to bloat asstable foams are rapidly produced from certain clover proteins.

At the present time bloat may be prevented by daily administration of asurfactant to the animal, for example, in the form of a drench.

That method of prevention, however, is only truly practicable with dairycattle since the cattle are brought in daily for milking; even herethere is considerable farmer resistance to drenching because of theadditional handling of the animals.

ln general, that method is not feasible for beef cattle and thus thereis a need for a prophylactic which can be administered to beef cattle atthe commencementof the bloat season in order to allow the cattle to takeadvantage of lush pastures.

It is known to employ a variety of heavy pellets for prophylaxis inruminant animals, for example, for correcting cobalt deficiency. Thesepellets rely upon their size and density so that they will remain withinthe rumen and upon their chemical composition for gradual dissipation ofthe active agent. It is difficult to apply this principle to theprevention of bloat since surfactants have a relatively low density andmust be incorporated as a minor constituent in a large pellet weightedby a suitable inert material. The result is that very large quantities(3kg) of such pellets must be employed in order to furnish bloatprotection for about 3 months the period of the normal bloat season. Ifthe weighting material is not used so that a high concentration of agentcan be employed, it is found that such pellets can be readilyregurgitated.

According to this invention there is provided a device for administeringa therapeutic or nutrient substance to a ruminant over an extendedperiod of time, said device comprising a body portion containing orcomprising said substance and having a first configuration or beingadapted to be arranged in a first configuration, whereby it is adaptedto be administered per os so as to pass into the rumen and being adaptedto change in the rumen into a second configuration which will prevent orat least hinder regurgitation of the device, whereby the device isretained in the rumen.

In one aspect, the device comprises a body portion which, by virtue ofits nature, construction or composition, is adapted to be arranged in afirst configuration whereby the device can be administered to a ruminantper os so as to pass into the rumen and, in the rumen environment, tochange into a second configuration as above mentioned.

In this aspect of the device, the body portion may comprise for examplea substantially insoluble, resilient matrix material which contains orcomprises a material to be released in the rumen. Such a material may beretained in the matrix material in the form of a suspension, solidsolution or the like. Alternatively it may be weakly chemically bondedto the matrix material.

ln a particular example of this aspect of the device, the body portionmay consist of a gel comprising a material to be released in the rumen.

Such a gel may be moulded or otherwise formed into a body portion of asuitable shape whereby it is adapted to be arranged in said firstconfiguration and, in the rumen environment, to change into said secondconfiguration as above mentioned. The gel may contain gelling agents andother components required to obtain the desired mechanical properties.

Suitable shapes into which the body portion may be formed include, forexample, shapes which may be termed doughnut-shaped" (i.e. toroidal) andboomerang-shaped" (i.e. angular) and other similar shapes. Preferablythe device is "doughnut-shaped."

In this particular aspect, the material to be released in the rumen maybe one or more non-ionic surfactant compounds.

The preferred surfactants are block copolymers of polyoxypropylene andpolyoxyethylene, such as those manufactured under the trade namePluronic, especially types L62, L62 and L64 thereof. Otherpolyoxyalkylenes and copolymers thereof are also suitable, as arepolyoxyethylene alcohols (sometimes called polyoxyethylene alkylethers), i.e., consisting of straight or branched long chain alcoholscondensed with ethylene oxide with or without end groups formed bycondensation with propylene oxide. The condensation products ofdodecanol with'6, 8, 10 or 12 moles of ethylene oxide are preferredmembers of this class.

Another type of surfactants which may be used is the polyoxyethylenealkylphenyl ethers, for example the condensation products of nonyloroctyl-phenol with 8 or 9 moles of ehtylene oxide, or with 9 to ll molesof ethylene oxide followed by 9 to l 1 moles of propylene oxide.

The preparation and properties of the abovedescribed substances are wellknown in the art and will not be described herein.

The gelling agent may be of any suitable known type; ethyl cellulose isone example but the art discloses many other suitable substances.

In order to obtain a matrix material having the desired properties, thegel suitably contains at least 3 percent by weight, and preferably 6 to15 percent by weight, of the gelling agent.

In another aspect, the device comprises at least one container portionand at least one obstructing means associated therewith, saidobstructing means being arranged in a first position relative to thecontainer portion to allow the device to be administered to a ruminantper os so as to pass into the rumen but which, in the rumen environment,moves or is caused to move relative to the container portion to a secondposition thereby to change the device into a second configuration asmentioned above.

The obstructing means may comprise for example one or more protruding orprotusible structures attached to or formed integrally with thecontainer portion and arranged so that (a) it may be positioned adjacentto the container portion, preferably more or less in conformity with theshape of the container portion, for passage of the device into therumen, and (1)) once in the rumen it can be caused or allowed to extendor protrude from the container portion and thereby obstruct or at leasthinder passage of the device out of the rumen.

Thus the obstructing means may comprise one or more flaps, tabs, flangesor like projections, or loops, bubbles, blisters or like protuberances.

In an extension of the latter aspect, the obstructing means may compriseone or more further container portions. Thus in yet another aspect ofthe invention, the device comprises at least two inter-connectedcontainer portions which" are arranged relative to one another in afirst configuration to allow the device to be administered to a ruminantper os so as to pass into the rumen thereof, and which, in the rumenenvironment, may be caused or allowed to move relative to one another tochange the device into a second configuration as above mentioned. Inthis form of the device the container portions generally will beconnected together by some connecting means which may take the formeither of a simple hinge or like member==-which permits the containerportions to move relative to one another but to remain essentiallyadjacent or it might comprise a member such as a web, string or rodwhich permits the container portions to separate from one another whilststill remaining connected. In the latter case, it is preferred that theconnecting member is at least semirigid and capable of holding thecontainer portions in the separated configuration.

Means may also be provided to positively assist or bring about thechange in configuration of the device within the rumen environment. Suchmeans may com prise the obstructing means or connecting means broadlydescribed above or may consist of additional biasing means. For example,the obstructing or connecting means may be made of a suitable resilientmaterial and arranged so that normally the obstructing or connectingmeans is biased towards its extended or protuberant position by virtueof its resilience. Alternatively the same function may be achieved byattaching the obstructing or connecting means to its respectivecontainer portion by a hinge of resilient material or by a passive hingeprovided or associated with biasing means.

The biasing means may be any suitable elastic or resilient material suchas natural or synthetic elastomers or resilient synthetic resins, forexample, natural or synthetic rubber, semi synthetic plastic materialssuch as cellulose esters, synthetic plastic materials such as thepolyamides including nylon, polyethylene terephthalate, polyethylene andother similarly resilient materials or an elasticized cloth.

The means provided to assist or bring about the change in configurationof the device in the rumen environment may also be a strip comprised ofa length or hydrophobic material and a length of hydrophobic materialbonded or otherwise connected together. In the presence of moisture,such strips will deform as a result of expansion or contraction of thehydrophilic material. Such strips will hereinafter be referred to as"hydrophilic/hydrophobic strips. Alternatively, the means may be a stripor piece of a material which shrinks in the rumen environment.

Hydrophilic materials suitable for use in the hydrophilic/hydrophobicstrips described above include cross-linked polydextrans, gelatintreated with formalin and cross-linked polyvinylalcohols. Suitablehydrophobic materials include water-insoluble polymers such as P.V.C.,polyethylene and nylon.

A suitable material which shrinks in the rumen environment iscross-linked polyvinal alcohol. This material, if stretched when fullyswollen with water and allowed to dry in the stretched state, willshrink when placed in the rumen environment.

Generally on administration the device will be held in the firstconfiguration, by the throat of the animal but, if desired, restrainingmeans may be provided which, in the rumen environment, are released toallow the device to move or be caused to move into the secondconfiguration which will prevent or at least hinder passage of thedevice out of the rumen.

The restraining means may be or comprise any material which isdissolved, destroyed, ruptured or broken in the rumen environment.Suitable materials from which the restraining means may be made includegelatin string, gelatin tape and water-soluble adhesives.

As it is sometimes desirable to provide for the regurgitation of thedevice (if indigestible) by the animal, it is also preferred that theconnecting means or hinge of the previously described embodimentscomprise at least one soluble, corrodible or frangible element, which,after the device has ended its functional life, will dissolve,disintegrate or fracture to allow the device to fragment into smallersections which are more readily regurgitated by the animal. For example,the hinge may be provided with a soluble or corrodible pin or secured tothe container portion by a clip, button, link or trigger made of acorrodible or slowly soluble material. Suitable materials for thispurpose will be obvious but by way of example there may be mentionedpoly (vinyl alcohol), proteinaceous materials, e.g. casein, magnesuimand its alloys, iron, steel and other corrodible metals.

In a further aspect of the device, the actual containers by solid orsemi-solid blocks comprising or consisting of the active substance.Where the substance to be released in the rumen is contained in one ormore con tainer portions, the device is normally constructed so that thematerial contained therein is released over an extended period of time.This may be achieved in a number of ways. For example, this material maybe enclosed in a number of capsules having differing solubility in rumenliquor. Tablets of the material may be coated with other materialshaving differing solubility in rumen liquor. The container portions ofthe device may be permeable in whole or in part to the material or torumen liquor, the permeability and amount of permeable material beingsuch that the material contained in the container portions will bereleased into the rumen at the desired rate. Sustained release of asolid material may be achieved by using the material in the form ofasparingly soluble solid, the rate of dissolution of which gives therequired rate of release of the material. The solid may be contained inthe device behind an insoluble gauze, for example, of nylon, or aperforated or slotted plate of the container materials. Where thematerial to be released is a corrodible solid (for example magnesiummetal for the control of grass tenany, as described hereinafter), it ispreferred that the material is in the form of a hollow half-cylinder.This has the advantage that reduction in the surface area by corrosionfrom the outside or inside cylindrical surfaces is kept to a minumumthroughout the lifetime of the device.

When liquid surfactants are to be administered by use of a deviceaccording to the invention having one or more container portions, it ispreferred that sustained release is obtained by using the surfactant inthe form of a gel, as has already been described. Other methods includeencasing the surfactant in a permeable, water-insoluble materials havingcapillaries or interconnecting pores extehding through them and paper orcloth partially impregnated with water-insoluble polymers such ascellulose acetate or polystyrene to reduce the permeability. Suchpermeable materials may be protected by water-destructable coatings.Films comprising water-soluble and water insoluble materials in whichthe water-soluble material will dissolve away in the rumen environmentto make the film permeable, may also be used. Examples of such films arefilms of ethyl and methyl cellulose, the latter being soluble, and filmsof cellulose esters such as the acetone and poly (dimethylaminoethylmethacrylate) or poly (tertbutylaminoethyl methacrylate) the lattermaterials being soluble in acids.

Materials which may be administered by use of the device according tothe invention include not only liquid surfactants as mentioned above,but also other medicaments, dietary suppliments or concentratednutrients, or combinations of any two or more of these materials.Examples of medicaments which may be administered include antibiotics,sulpha drugs, sedatives, anthelmintics, antipyretics, hormones,hypoglycemic agents, antispasmodics and hematics. Furthermore, thedevice may be used to release rumen-by-pass" materials. These materialscomprise an active material which has a coating of, or is incorporatedin a matrix of, a polymeric material which is unaffected in the rumenenvironment, but which is attacked and dissolved as the materials passfurther down the digestive tract of the ruminant.

Suitable polymeric materials include polymers of formaldehyde or itscondensation product, with amines and/or amides, polymers and copolymcrsof certain of the N-alkyl amino aIkyl-acrylates, -methacrylates,-acrylamides and -methacrylamides and cyclic imides of copolymers ofmaleic anhydride and styrene, which are insoluble in the rumenenvironment.

As indicated above, the device may be used to prevent disorders ofruminants other than bloat. Such disorders include hypomagnesemia (grasstetany), hypocalcaemia (milk fever) and acetonaemia (ketosis, grassfever).

Hypomagnesemia and grass tetany are both manifestations of magnesiumdeficiency. They can occur in cattle, particularly during the earlystages of lactation, when the daily intake of magnesium with their dietis less than the demands imposed by milk production. Administration ofsufficient magnesium to prevent hypomagnesemia (l to 3 g/day) generallyelliminates the more severe milk fever. Both disorders may be manifestover the whole of the lactation period, but treatment with a magnesiumsupplement during the first 8 to 12 weeks is generally considered to beadequate in most cases. The use of the devices herein described forsupplying supplementary magnesium is not restricted by the requirementof a high density as are the known pellets for preventing thesedisorders. Consequently, a wider selection of magnesium compounds aspotential prophylactics may be made. For example, magnesium oxide(periclase), hydroxide (brucite) laurate, oxalate, and other compoundsor mixtures of compounds may be used to provide the required dailysupplement of magnesium.

It will be appreciated that while passage of the presently known pelletsform the rumen further down the digestive tract does not appear to belikely, the configuration to which a device according to the inventionis changed in the rumen environment will also prevent or hinder passageof this device further down the digestive tract.

The present invention also extends to methods of treating ruminantswhich comprise the steps of administering to the ruminant, per 0s, adevice according to the invention or a plurality of such devices.

Several examples of devices in accordance with this invention will nowbe described with reference to the accompanying drawings in which:

FIG. 1 is an exploded perspective view of one half of a preferred formof the device;

FIG. 2 is an end elevation and FIG. 3 is a sectional view of the deviceof FIG. 1, in the first and second configurations respectively;

FIGS. 4 and 5, 6 and 7, 8 and 9 are sectional views of other devices inthe first and second configurations respectively;

FIGS. 10 and ll, 12 and 13 are plan and sectional views of anotherembodiment in the first and second configurations, respectively.

The first configuration of the devices refers to that configuration inwhich they are adapted to be passed via the oesophagus of a ruminantinto the rumen, and the second confuguration to that adopted once in therumen.

The device shown in FIGS. I to 3 comprises a body position formed of twoboat-like semi-cylinders 1 which are 6 inches to 7 inches long and havesemihemispherical ends. When placed together they form a 1 /2 inchdiameter cylinder with rounded ends, and having two filling spouts 2.

The semi-cylinders are made of an impermeable and water-insolublepolymer, such as cellulose acetate, polypropylene or polyethylene. Theymay, if desired, be reinforced with paper or other fibers, or cloth.

The flat face of each semi-cylinder l, is comprised by a plate 3 havinga half-inch slot 4 therein, provided with a curved inwardly directed lip5.

The plate 3 also has a projecting tab 6 provided with a slot 7. A malehinge member 8 and a female hinge member 9 are attached to or mouldedintegrally with the edge of the plate 3 carrying the tab 6. The malehinge member 8 comprises an outwardly projecting spigot 8A carrying ashort pin 88. The female hinge member 9 comprises a spaced pair ofspigots 9A having pin-receiving slots 9B in their outer ends.

As shown in FIG. 3, the device is also provided with a trigger mechanismcomprising corrodible metal washer 10 attached to the outside wall ofeach semicylinder I by an expanded spigot 11. A circumferential groove12 runs from the spigot 11 around the semicylindrical face of eachsemi-cylinder 1. A hinge link 13 (FIGS. 1 and 3) is provided to securethe two semicylinders I together. The link 13 consists of a strip offlexible plastics material having thickened end portions 13A with a hole13B therein. If desired a narrow slit 13C may be provided between thehole 138 and and edge of the strip to facilitate assembly of the deviceas described hereinafter. In an alternative form of the link shown as113 two holes 1138 are provided, each with a slit 13C, communicatingwith edges of the strip. In use two semi-cylinders I are securedtogether as shown in FIG. 3 by inserting the male hinge members 8 in thefemale hinge members 9. The link 13 is bent to a U- shape and one endportion is passed through the slot 7 in each semi-cylinder 1. One end ofa band 14 of an elastic material, e.g. rubber, is looped around thespigot 11 and under the washer on one of the semicylinders 1. The band14 is passed along the groove 12 through the holes 1313 in each end ofthe link 13 and then along the groove 12 of the other semi-cylinder andthe other end of the band is looped around the spigot 11 of the othersemi-cylinder.

Each of the semi-cylinders contains about 100 ml. of gelled Pluronic L62(see Example 1). Other suitable antifoaming agents include polypropyleneglycols, Pluronic" L61 and L64, and products produced by condensing longchain alcohols with ethylene oxide, e.g., lauryl alcohol condensed with6 to 12 moles of ethylene oxide.

As shown in FIG. 2 the cylinders may be folded together to form anessentially cylindrical structure against the tension of the band 14.The device may be retained in this configuration by means ofa band ofsoluble material e.g., a gelatin tape, or alternatively the constrictionof the oesophahus in the animal may be sufficient to provide thenecessary restraint during administration. Once in the rumen the deviceopens to the configuration shown in FIG. 3 thus allowing the contents ofthe rumen to Contact the material contained in the semi-cylindersthrough the slot 4.

The washers 10 are made of magnesium or any similar corrodible metal andare proportioned so that at some time after the contents of the devicehave been released the pins will corrode to such an extent that theywill release the ends of the band 14 from the spigots II. The band 14can then pull free of the link 13 which in turn can become detached fromthe slots by the natural movement of the device within the rumen.

The hinge members 8, 9 can then detach and the animal can regurgitatethe individual semi-cylinders.

In an alternative arrangement the semi-cylinders I are filled withliquid Pluronic L62 or the like, and the flat faces are closed by asheet of porous paper impregnated with cellulose acetate to reduce itspermeability. Other permeable materials or materials adapted to becomepermeable which could be used have previously been listed.

The device shown in FIGS. 4 and 5 is similar to the one shown in FIGS. 1to 3, except that it has a body portion formed of hemi-cylinders 21which are closed on their straight sides and are made of permeablematerial or material adapted to become permeable. In lieu of hinges andelastic bands, the hemi-cylinders 21 are connected to two hydrophilic/hydrophobic strips 22 and as shown in FIG. 4 are secured together bymeans of a gelatin tape 23. In the rumen, the gelatin tape 23 dissolvesand the strips deform to the configuration shown in FIG. 5, thereby toprevent or hinder regurgitation of the device.

A similar device can be constructed with three lobes which together makeup a cylinder. In a further modification, elastic hinges, which have arest position similar to that shown in FIG. 5, and are deformed to aconfiguration similar to that shown in FIG. 4 to allow the device topass via the oesophagus into the rumen, may replace thehydrophilic/hydrophobic strips.

The device shown in FIGS. 6 and 7 is particularly suitable foradministering solid substances such as magnesium metal or gelledPluronic surfactants. The two hemi-cylinders 31 are joined by an elastichinge member 32 made out of nylon. The rest position of the hinge is asshown in FIG. 7, but it is deformed into the configuration shown in FIG.6 to allow the device to pass via the oesophagus into the rumen. Agelatin tape 33 may be positioned as shown to secure the device in theconfiguration.

The devices shown in FIGS. 8 and 9 consist ofa body portion formed of acylinder 41 having two substantially rigid, hemicylindrical wings" 42,43 respectively attached to the cylinder 41. Preferably, both thecylinder 41 and the wings 42, 43 have rounded ends. The cylinder 41 ismade of permeable material or has slots to allow release of the activematerial. The wings 42, 43 are initially folded so as to fit closelyaround the cylinder 41, as shown in FIG. 8, to allow the devices to passvia the oesophagus into the rumen. There, the gelatin tape 44 dissolvesand the devices are changed to the configuration shown in FIG. 9,thereby to prevent or hinder regurgitation.

The device shown in plan in FIGS. 10 and 12 and in cross section inFIGS. 11 and 13, comprises a body portion 51 of a substantiallyinsoluble resilient matrix material incorporating a material to bereleased in the rumen, moulded or otherwise formed into a doughnutshapeas shown in FIGS. 12 and 13. The body portion 51 may for example have anoverall diameter of 4 inches, the diameter of the inside cutaway portionbeing 2.8 inches and the maximum thickness 0.6 inches. This device,before administration to the ruminant is deformed to the configurationshown in FIGS. 10 and 11 and held in that configuration by gelatin tapes52. When the device in this configuration is passed into the rumen, therumen liquor causes the gel atin tape 52 to dissolve and the device,because of the resilience of the body portion, reverts to theconfiguration shown in FIGS. 12 and 18 thereby to prevent or hinderregurgitation of the device.

A suitable material from which the body portion 51 may be formed may beprepared by heating a liquid surfactant with 8 percent by weight ofethyl cellulose to a temperature of C. to form a clear solution. Thisclear solution is poured into a suitable mould and cooled to form arubber-like solid. A body portion formed in this way releases thesurfactant slowly from the matrix material into the rumen environment.Liquid surfactants which may be incorporated into a matrix material inthis way include the Pluronics L62 and L64 and the product formed bycondensing 1 mol. of nonyl phenol with 11 mols. of ethylene oxide andfurther condensing the thus produced product with 11 mols. of propyleneoxide.

The following examples show the use of some of the above describeddevices.

EXAMPLE 1 Plastic cylindrical capsules 150 mm long and 30 mm diameter,made up of two half-cylinders hinged along one edge, were constructed.The hinges were of rubber and were biased so that two half-cylinderswould spring apart in the rumen and thus expose fiat surfaces of thehalf-cylinders through which the agent in the capsule could diffuse intothe rumen. The hinges were constructed so that, under the rumenconditions, they would pull away from the half-cylinders after effectiverelease of the agent, thereby facilitating regurgitation of thefragmented devices.

The capsules were filled with a gel of Pluronic L62 (90 percent) andethyl cellulose percent). Release of the surfactant from the gel wasrestricted by 90 X 130 mm slots in the flat face of the capsules.

A commercial herd of 46 milking cows, predominantly Jersey, were treatedwith two capsules each. Thirty further cows of the same herd weredrenched at the evening milking with 7.5 ml ofPluronic" L64. The cowsgrazed on irrigated pasture, predominantly white clover (Trifoliumrepens). Bloat was assessed visually, scores 1 to 3 being (1) left flankdistended, (2) both flanks distended, and (3) in need of immediatetreatment. The trial lasted for 28 days.

Preliminary experiments showed that half-cylinders and un-openedcapsules of the quoted dimensions were regurgitated less than 48 hoursafter administration. The rate of release of surfactant from thecapsules was approximately proportional to the amount remaining in thecapsule, the half-life being 42 days. The mean release was og/cow/day.

No bloat was observed in the animals treated with the capsules duringthe first four days of the trial, whilefive cases of bloat were recordedfor the drenched cows. Over the trial period 76 percent of the animalstreated with the capsules and 47 percent of those drenched had bloated.Of the total number of bloated cases observed in the treated animals, 6percent occurred during the first 9 days, 24 percent during the nextfifteen days and 70% during the final four days. The correspondingproportions in the drenched animals were 31 percent, 48 percent and 2|percent.

Regurgitated fragments of capsules were recovered in the fields from thefirst day after treatment; 34 halfcylinders and 9 smaller fragments werefound. One intact capsule was found after the experiment concluded.

While these trials indicate some degree of success it was consideredthat the hinges of the capsules failed too quickly leading to prematureregurgitation. However, it was clear that release of the surfactant fromthe retained capsules continued for about 25 days.

EXAMPLE 2 The experiment of Example l was repeated using capsules withstrengthened hinges.

In this case 50 cows of the same herd as in Example 1 were treated withtwo of the devices and 16 further cows of the same herd were keptovernight in pastures sprayed with anti-bloat oil. The conditions of theexperiment were similar to those of Example 1 and the trial lasted 36days.

In the animals treated with the capsules, no bloat occurred during thefirst l 1 days while 30 cases were recorded for the animals on thesprayed pasture. Over the trial period percent of the treated animalsand 88 percent of those on spray pasture bloated.

The incidence of severe bloat (i.e. that requiring treatment ofdrenching with oil) per 1,000 cow-days, in the animals treated with thecapsules was reduced to 1 percent of that for the control animals overthe first 32 days. The surfactant in the capsules was exhausted by the36th day.

Five complete capsules and 3 fragments were recovered in the field overthe trial period.

These results show that with a correctly constructed capsule substantialprotection of cows against bloat can be achieved for extensive periods,and no treatment is required other than the initial administration ofthe capsules.

It is to be realised that modifications and adaptions may be made to theconstructions specifically described above. For instance, use may bemade of semipermeable materials to cause configuration changes byosmotic swelling. Accordingly, all such modifications and adaptions areto be considered as falling within the spirit and scope of thisinvention which includes every novel feature and combination of featuresdisclosed herein.

The claims defining the invention are as follows:

1. A device for insertion into the rumen of a ruminant through theesophagus and adapted to be retained within the rumen for free movementtherein over an extended period of time, said device comprising a bodycontaining an effective amount of a therapeutic or nutrient substance ofa type normally administered to a ruminant per os, a major proportion ofsaid body consisting of said substance, said body having a compressedconfiguration and an expanded configuration, the compressedconfiguration permitting the passage of the device through the esophagusinto the rumen and the expanded configuration being one which willsubstantially retard passage of the device through the esophagus butwill still permit substantially free movement of the device within therumen, means for resiliently urging said body from said compressedconfiguration to said expanded configuration, restraining meansdissolvable in the rumen holding said body in said compressedconfiguration until it is received within the rumen whereby said devicein compressed configuration may be administered per os so as to passinto the rumen and will expand in the rumen so as to hinderregurgitation during the period of treatment, and means for holding saidsubstance in said body and for slowly releasing said substance from saidbody when said body is in the rumen.

2. A device as claimed in claim 1 wherein said substance is a bloatcontrol agent.

3. A device as claimed in claim 2 wherein a major proportion of saidbody consists of a bloat control agent.

4. A device as claimed in claim 2 wherein said body contains a gelformed from said bloat control agent and a gelling agent.

5. A device as claimed in claim 4 wherein said bloat control agent is apolyoxyalkylene surfactant and said gelling agent is ethyl cellulose.

6. A device as claimed in claim 4 wherein said gel contains from about 3to 15 percent by weight of the gelling agent and the remainder of thegel consists es sentially of the bloat control agent.

7. A device as claimed in claim 2 wherein said bloat control agent is apolyoxyalkylene surfactant.

8.,A device as claimed in claim 2 wherein said bloat control agent isselected from the group consisting of block copolymers ofpolyoxypropylene and polyoxyethylene and condensation products ofdodecanol with 6 to l2 moles of ethylene oxide.

9. A device as claimed in claim 1 wherein said substance is a magnesiumsupplement.

10. A device for administering a therapeutic or nutrient substance to aruminant over an extended period of time, said device comprising aresilient, permeable body which will allow passage of the substance tobe administered and which is of essentially toroidal form having acompressed configuration which will permit passage of the device intothe rumen through the esophagus of the ruminant and an expandedconfiguration toward which it is resiliently urged which will retardpassage of the device from the rumen but will still permit substantiallyfree movement of the device in the rumen, and restraining meansdissolvable in the rumen holding said body in said compressedconfiguration whereby said device may be administered per os forexpansion and retention in the rumen during the period of treatment.

11. A method for the administration of a therapeutic or nutrientsubstance to a ruminant over an extended period of time comprisingincorporating said substance in a device from which it is releasable inthe rumen of a ruminant, said device having a first configuration inwhich it is held by restraining means and a second configuration intowhich it is resiliently urged, said restraining means being renderedineffective in and by the rumen environment to hold said device in thefirst configuration in the rumen, the first configuration permittingpassage of the container into the rumen through the esophagus of theruminant and the second configuration being one which will hinderpassage of the container from the rumen but will still permitsubstantially free movement of the container within the rumen, holdingsaid container in said first configuration by said restraining means andadministering it to the ruminant per os so as to pass into the rumenwhere the restraining means is rendered ineffective to hold the devicein the first configuration and the device assumes the secondconfiguration for retention in the rumen during the period of treatment.

12. A device for administering a therapeutic or nutrient substance to aruminant over an extended period of time, said device comprising a bodyportionof which a major proportion comprises said substance, said bodyportion having a first configuration into which it may be urged foradministration per os so as to pass into the rumen and a secondconfiguration which it will assume in the rumen and which will hinderregurgitation of the device but will still permit substantially freemovement in the rumen, and restraining means for holding said bodyportion in said first configuration until it passes into the rumen, saidrestraining means being rendered ineffective in and by the rumenenvironment to hold said body portion in the first configuration in therumen and to permit said body portion to assume said secondconfiguration in the rumen.

13. A device for administering a therapeutic or nutrient substance to aruminant over an extended period of time, said device comprising a bodyportion of which a major proportion comprises said substance, said bodyportion having first configuration into which it may be urged foradministration per 05 so as to pass into the rumen and a secondconfiguration which it will assume in the rumen and which will hinderregurgitation of the device but will still permit substantially freemovement in the rumen, and restraining means for holding said bodyportion in said first configuration until it passes into the rumen, saidrestraining means being destroyed in the rumen environment to permitsaid body portion to assume said second configuration in the rumen.

14. A device as claimed in claim 13 wherein said body portion comprisesat least one container portion and at least one obstructing meansassociated therewith, said obstructing means being movable into a firstposition relative to said container portion to provide said firstconfiguration to allow the device to be administered to a ruminant peros so as to pass into the rumen and, in the rumen environment, movablerelative to the container portion to a second position thereby to changesaid body into said second configuration.

15. A device as claimed in claim 14, wherein the obstructing meanscomprises at least one protruding structure attached to the containerportion.

16. A device as claimed in claim 14 wherein the obstructing meanscomprises at least one further container portion.

17. A device as claimed in claim 14, wherein the obstructing means isattached to the container portion by a corrodible element which issusceptible to eventual destruction in the rumen environment, wherebyafter the device has ended its functional life the destruction of theelement will allow fragmentation of the device.

18. A device as claimed in claim 13, wherein said body portion comprisesat least two inter-connected body portions which are movable relative toone another into said first configuration to allow the device to beadministered to a ruminant per os as to pass into the rumen thereof, andwhich, in the rumen environment, move relative to one another to changethe device into said second configuration.

1. A device for insertion into the rumen of a ruminant through theesophagus and adapted to be retained within the rumen for free movementtherein over an extended period of time, said device comprising a bodycontaining an effective amount of a therapeutic or nutrient substance ofa type normally administered to a ruminant per os, a major proportion ofsaid body consisting of said substance, said body having a compressedconfiguration and an expanded configuration, the compressedconfiguration permitting the passage of the device through the esophagusinto the rumen and the expanded configuration being one which willsubstantially retard passage of the device through the esophagus butwill still permit substantially free movement of the device within therumen, means for resiliently urging said body from said compressedconfiguration to said expanded configuration, restraining meansdissolvable in the rumen holding said body in said compressedconfiguration until it is received within the rumen whereby said devicein compressed configuration may be administered per os so as to passinto the rumen and will expand in the rumen so as to hinderregurgitation during the period of treatment, and means for holding saidsubstance in said body and for slowly releasing said substance from saidbody when said body is in the rumen.
 2. A device as claimed in claim 1wherein said substance is a bloat control agent.
 3. A device as claimedin claim 2 wherein a major proportion of said body consists of a bloatcontrol agent.
 4. A device as claimed in claim 2 wherein said bodycontains a gel formed from said bloat control agent and a gelling agent.5. A device as claimed in claim 4 wherein said bloat control agent is apolyoxyalkylene surfactant and said gelling agent is ethyl cellulose. 6.A device as claimed in claim 4 wherein said gel contains from about 3 to15 percent by weight Of the gelling agent and the remainder of the gelconsists essentially of the bloat control agent.
 7. A device as claimedin claim 2 wherein said bloat control agent is a polyoxyalkylenesurfactant.
 8. A device as claimed in claim 2 wherein said bloat controlagent is selected from the group consisting of block copolymers ofpolyoxypropylene and polyoxyethylene and condensation products ofdodecanol with 6 to 12 moles of ethylene oxide.
 9. A device as claimedin claim 1 wherein said substance is a magnesium supplement.
 10. Adevice for administering a therapeutic or nutrient substance to aruminant over an extended period of time, said device comprising aresilient, permeable body which will allow passage of the substance tobe administered and which is of essentially toroidal form having acompressed configuration which will permit passage of the device intothe rumen through the esophagus of the ruminant and an expandedconfiguration toward which it is resiliently urged which will retardpassage of the device from the rumen but will still permit substantiallyfree movement of the device in the rumen, and restraining meansdissolvable in the rumen holding said body in said compressedconfiguration whereby said device may be administered per os forexpansion and retention in the rumen during the period of treatment. 11.A method for the administration of a therapeutic or nutrient substanceto a ruminant over an extended period of time comprising incorporatingsaid substance in a device from which it is releasable in the rumen of aruminant, said device having a first configuration in which it is heldby restraining means and a second configuration into which it isresiliently urged, said restraining means being rendered ineffective inand by the rumen environment to hold said device in the firstconfiguration in the rumen, the first configuration permitting passageof the container into the rumen through the esophagus of the ruminantand the second configuration being one which will hinder passage of thecontainer from the rumen but will still permit substantially freemovement of the container within the rumen, holding said container insaid first configuration by said restraining means and administering itto the ruminant per os so as to pass into the rumen where therestraining means is rendered ineffective to hold the device in thefirst configuration and the device assumes the second configuration forretention in the rumen during the period of treatment.
 12. A device foradministering a therapeutic or nutrient substance to a ruminant over anextended period of time, said device comprising a body portion of whicha major proportion comprises said substance, said body portion having afirst configuration into which it may be urged for administration per osso as to pass into the rumen and a second configuration which it willassume in the rumen and which will hinder regurgitation of the devicebut will still permit substantially free movement in the rumen, andrestraining means for holding said body portion in said firstconfiguration until it passes into the rumen, said restraining meansbeing rendered ineffective in and by the rumen environment to hold saidbody portion in the first configuration in the rumen and to permit saidbody portion to assume said second configuration in the rumen.
 13. Adevice for administering a therapeutic or nutrient substance to aruminant over an extended period of time, said device comprising a bodyportion of which a major proportion comprises said substance, said bodyportion having first configuration into which it may be urged foradministration per os so as to pass into the rumen and a secondconfiguration which it will assume in the rumen and which will hinderregurgitation of the device but will still permit substantially freemovement in the rumen, and restraining means for holding said bodyportion in said first configuration until it passes into the rumen, saidrestraining means being destroyed In the rumen environment to permitsaid body portion to assume said second configuration in the rumen. 14.A device as claimed in claim 13 wherein said body portion comprises atleast one container portion and at least one obstructing meansassociated therewith, said obstructing means being movable into a firstposition relative to said container portion to provide said firstconfiguration to allow the device to be administered to a ruminant peros so as to pass into the rumen and, in the rumen environment, movablerelative to the container portion to a second position thereby to changesaid body into said second configuration.
 15. A device as claimed inclaim 14, wherein the obstructing means comprises at least oneprotruding structure attached to the container portion.
 16. A device asclaimed in claim 14 wherein the obstructing means comprises at least onefurther container portion.
 17. A device as claimed in claim 14, whereinthe obstructing means is attached to the container portion by acorrodible element which is susceptible to eventual destruction in therumen environment, whereby after the device has ended its functionallife the destruction of the element will allow fragmentation of thedevice.
 18. A device as claimed in claim 13, wherein said body portioncomprises at least two inter-connected body portions which are movablerelative to one another into said first configuration to allow thedevice to be administered to a ruminant per os as to pass into the rumenthereof, and which, in the rumen environment, move relative to oneanother to change the device into said second configuration.